This study aimed to investigate the mechanism of compound Agrimonia pilosula enteritis capsules (CAPEC) on ulcerative colitis (UC) in mice with dampness-heat syndrome. The mice were randomly divided into five groups: the control group, the model group, the positive drug (5-aminosalicylic acid, 5-ASA) group, the low-dose CAPEC (CAPEC-L) group and the high-dose CAPEC (CAPEC-H) group. The mice models were established by using high-fat high-sucrose diet, feeding with distilled spirit and dextran sulfate sodium (DSS). The effects of CAPEC on bile acids (BAs) metabolic profiles in bile and the FXR-SREBP-1 signaling pathway were investigated in the model of UC in mice with dampness-heat syndrome by ELISA, qRT-PCR, UHPLC-QQQ/MS, and histopathological analysis. The results showed that, compared with the model group, the CAPEC-L group and the CAPEC-H group significantly reduced the disease activity index (DAI), and proinflammatory cytokine levels (including IL-6, IL-1β, and TNF-α) in both serum and colon tissues. Additionally, CAPEC markedly ameliorated intestinal inflammation, hepatic lipid accumulation, and pathological alterations in tongue tissue. The CAPEC-H group significantly attenuated the abnormal elevation of BAs profiles in bile, and up-regulated hepatic mRNA levels of Cyp7a1, Cyp7b1, Cyp27a1, Bsep, Fxr, and Shp, while down-regulating Srebp-1 and Cyp8b1 expression. The experimental results suggest that CAPEC alleviates UC with dampness-heat syndrome by ameliorating BAs metabolic disorders, hepatic lipid accumulation, and intestinal inflammation. These findings provide mechanistic insights into CAPEC’s traditional effects of clearing heat and drying dampness, and strengthening the spleen to relieve diarrhea.

AIM: To investigate the prevalence of pterygium in the southeast coastal area, analyze associated risk factors, and develop a multimodal machine learning predictive model.METHODS:A cross-sectional epidemiological study. A random sampling of the resident population of the Zhoushan Islands was performed. Data were collected through on-site ophthalmic examinations and epidemiological surveys. Univariate and multivariate analyses were performed to identify risk factors associated with pterygium. A multimodal artificial intelligence machine learning model was constructed to integrate and analyze both structured and unstructured data for predictive modeling. RESULTS:A total of 1 842 participants were enrolled in this study, including 926 males(50.27%)and 916 females(49.73%), with a mean age of 48.62±10.35 y. A total of 644 patients(34.96%), including 323 males(50.15%)and 321 females(49.84%)were diagnosed with pterygium, including 502 cases(77.95%)were unilateral, and 142 cases(22.05%)were bilateral. There were 1 198 cases without pterygium, including 603 males(50.33%)and 595 females(49.67%). Occupation, daily outdoor sunlight exposure duration, meibomian gland orifice obstruction, age, smoking, and alcohol consumption were identified as significant risk factors for pterygium. Occupation and daily outdoor sunlight exposure duration were the most potent risk factors(OR=6.125, P<0.001; OR=5.348, P<0.001, respectively), followed by age >40 y(OR=5.295, P<0.001)and meibomian gland orifice obstruction(OR=5.248, P<0.001). The multimodal machine learning model demonstrated good predictive performance, as evidenced by the receiver operating characteristic(ROC)curve, precision-recall(PR)curve, and confusion matrix, all indicating high predictive value, AUC=0.86, AP=0.77.CONCLUSION: Fishermen and farmers aged over 40 y with more than 4 h of daily sunlight exposure are at high risk for pterygium in the southeast coastal area. Meibomian gland dysfunction is correlated with corneal invasion of pterygium and may facilitate its progression; therefore, active health education and targeted intervention are recommended. The multimodal machine learning model provides accurate and reliable predictive capability for pterygium risk, which may facilitate risk stratification and early warning for pterygium in southeast coastal populations.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

AIM:To investigate the mechanism of action of Tamarix chinensis Lour.on streptozotocin-induced type 2 diabetes mellitus(T2DM)through network pharmacology,molecular docking and ex-perimental validation.METHODS:Using the TCSMP database and Swiss Target Prediction tools screen the active components and predict potential tar-gets in Tamarix chinensis Lour..Retrieving potential disease targets associated with T2DM from data-bases such as GeneCards,OMIM,and DisGeNET.The intersection targets of Tamarix chinensis Lour.and T2DM disease was obtained through Venny platform.The STRING database was used to con-structed PPI network,and Cytoscape 3.8.0 soft-ware was use to visualized.GO function enrich-ment and KEGG pathway enrichment analysis were performed through the Metascape database.Dock-ing of important target proteins and compounds was carried out by AutoDock software.SPF grade male rats were randomly divided into normal group,model group,MET group(88.5 mg/kg),TE high-dose(800 mg/kg)group,TE medium-dose(400 mg/kg)group and TE low-dose(200 mg/kg)group(n=10).High-fat and high sugar feed com-bined with low dose STZ(45 mg/kg)was used to in-duce T2DM rat model,and the rats were adminis-tered orally for 5 weeks.Fasting blood glucose(FBG),insulin(FINS)level and HOMA-IR index,bio-chemical indicators[superoxide dismutase(SOD),malondialdehyde(MDA),glycosylated hemoglobin A1c(HbA1c)and inflammatory factor[interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α),vascu-lar cell adhesion molecular(VCAM-1)levels of the rats were also observed;morphological changes of renal tissue was observe by HE staining.RESULTS:Based on the screening conditions of oral bioavail-ability(OB)≥ 30％and drug like properties(DL)≥0.18,a total of 19 main active ingredients with po-tential therapeutic effects on T2DM were screened from Tamarix chinensis Lour.,including ergosta-5,24(28)-dien-3,7,16-triol,quercetin-3,3'-dimethyl ether,kaempferol,quercetin,and others.By analyz-ing the potential targets of Tamarix chinensis Lour.for treating T2DM,a total of 185 potential target genes were screened,including SRC,EGFR,HSP90AA1,AKT1,ESR1,H1F1A,TNF,PIK3R1,etc,in-volving cancer signaling pathways,insulin resis-tance,MAPK signaling pathways,PI3K Akt signaling pathways,etc.Molecular docking results showed that the binding energies were all less than-5.0 kcal/mol,indicating that a strong binding abili-ty between the active ingredients screened by Tam-arix chinensis Lour.and the potential targets for the treatment of T2DM.The animal experiment re-sults showed that compared with the model group,the weight loss of rats in the MET and TE groups was slowed down,and the levels of FBG,FINS,MDA,HbA1c,IL-1β,TNF-α,VCAM-1,HOMA-IR in-dex were reduced,the SOD level was increased,and the differences were statistically significant(P＜0.05,P＜0.01),Renal tissue cellular morphology also showed notable improvement.Most importantly,all these results demonstrating dose-dependent ef-fects.CONCLUSION:Tamarix chinensis Lour.dis-plays a significant therapeutic effect on T2DM through multi-component,multi-target,and multi-pathway synergistic actions to improve blood glu-cose levels.The findings of this study provide a the-oretical basis for the clinical application of Tamarix chinensis Lour.in the treatment of T2DM.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Diffuse large B-cell lymphoma(DLBCL)is a highly heterogeneous disease.Although standard first-line regimens can cure＞50%of patients,approximately one-third of them develop relapsed/refractory DLBCL(r/r DLBCL).Consequently,immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL.The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment,antibody-based therapies have evolved rapidly,progressing from monoclonal antibodies(e.g.,rituximab,tafasitamab)to bispecific antibodies(e.g.,odronextamab,glofitamab,epcoritamab)and antibody-drug conjugate(e.g.,polatuzumab vedotin,loncastuximab tesirine).These engineered agents enhance immune cytotoxicity and tumor-specific targeting,providing novel therapeutic options for r/r DLBCL patients.